Urinary Proadrenomedullin and Disease Severity in Children With Suspected Community-acquired Pneumonia.

BACKGROUND: Plasma proadrenomedullin (proADM) is a promising biomarker to predict disease severity in community-acquired pneumonia (CAP). Urinary biomarkers offer advantages over blood, including ease of collection. We evaluated the association between urinary proADM and disease severity in pediatric CAP. METHODS: We performed a prospective cohort study of children 3 months to 18 years with CAP. Urinary proADM/creatinine (Cr) was calculated. Disease severity was defined as: mild (discharged home), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with supplemental oxygen and complicated pneumonia) and severe (eg, vasopressors and invasive ventilation). Outcomes were examined using logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP. RESULTS: Of the 427 children included, higher proADM/Cr was associated with increased odds of severe disease compared with nonsevere disease [suspected CAP, odds ratio (OR) 1.02 (95% confidence interval (CI) 1.003, 1.04); radiographic CAP, OR 1.03 (95% CI 1.01, 1.06)] when adjusted for other covariates. ProADM/Cr had an area under the receiver operating characteristic curve of 0.56 (threshold 0.9 pmol/mg) to differentiate severe from nonsevere disease in suspected CAP and 0.65 in radiographic CAP (threshold 0.82 pmol/mg). Healthy controls had less proADM in their urine (median, 0.61 pmol/mg) compared with suspected (0.87 pmol/mg, P = 0.018) and radiographic (0.73 pmol/mg, P = 0.016) CAP. CONCLUSIONS: Urinary proADM/Cr ratio measured at the time of emergency department visit was statistically associated with the development of severe outcomes in children with CAP, with stronger discriminatory performance in radiographic disease.

Effects of Sustained Inflation or Positive Pressure Ventilation on the Release of Adrenomedullin in Preterm Infants with Respiratory Failure at Birth.

OBJECTIVE: Delivery room (DR) management may play an important role in the development and prevention of lung injury. Therefore, in a cohort of low birth weight infants (LBW), we investigated the effects of two different lung recruitment maneuvers, such as positive pressure ventilation (PPV) and sustained inflation (SI) on adrenomedullin (AM), a well-established lung-specific vasoactive agent. STUDY DESIGN: This is a prospective case-control randomized study in 44 LBW infants spontaneously breathing with respiratory failure at birth requiring respiratory support. LBW were randomized to receive PPV (n = 22) or SI (n = 22) support. AM was measured from blood in samples collected at birth from arterial artery (BLT0) and at 1-hour (BLT1) and at 24-hour (BLT2) from peripheral venous site. AM assessment in urine samples was performed at 1-hour (URT1) and at 24-hour (URT2). RESULTS: No significant differences in AM (p > 0.05) blood (T0-T2) and urine (T1, T2) levels were observed between groups. CONCLUSION: The present data, showing the absence of any differences in AM blood and urine levels, suggest that PPV and SI are both feasible and equally effective DR maneuvers. The findings open the way to further studies evaluating the effects of PPV and SI on short-/long-term respiratory outcome through biomarkers assessment.

Failure of renal biomarkers to predict worsening renal function in high-risk patients presenting with oliguria.

PURPOSE: Oliguria is a common symptom in critically ill patients and puts patients in a high risk category for further worsening renal function (WRF). We performed this study to explore the predictive value of biomarkers to predict WRF in oliguric intensive care unit (ICU) patients. PATIENTS AND METHODS: Single-center prospective observational study. ICU patients were included when they presented a first episode of oliguria. Plasma and urine biomarkers were measured: plasma and urine neutrophil gelatinase-associated lipocalin (pNGAL and uNGAL), urine α1-microglobulin, urine γ-glutamyl transferase, urine indices of tubular function, cystatin C, C terminal fragment of pro-arginine vasopressin (CT-ProAVP), and proadrenomedullin (MR-ProADM). RESULTS: One hundred eleven patients formed the cohort, of whom 41 [corrected] had worsening renal function. Simplified Acute Physiology Score (SAPS) II was 41 (31-51). WRF was associated with increased mortality (hazard ratio 8.65 [95 % confidence interval (CI) 3.0-24.9], p = 0.0002). pNGAL, MR-ProADM, and cystatin C had the best odds ratio and area under the receiver-operating characteristic curve (AUC-ROC: 0.83 [0.75-0.9], 0.82 [0.71-0.91], and 0.83 [0.74-0.90]), but not different from serum creatinine (Screat, 0.80 [0.70-0.88]). A clinical model that included age, sepsis, SAPS II, and Screat had AUC-ROC of 0.79 [0.69-0.87]; inclusion of pNGAL increased the AUC-ROC to 0.86 (p = 0.03). The category-free net reclassification index improved with pNGAL (total net reclassification index for events to higher risk 61 % and nonevents to lower 82 %). CONCLUSIONS: All episodes of oliguria do not carry the same risk. No biomarker further improved prediction of WRF compared with Screat in this selected cohort of patients at increased risk defined by oliguria.

Urinary adrenomedullin level in children with acute pyelonephritis before and after treatment.

INTRODUCTION: Adrenomedullin (AM) is a 52-amino acid peptide that causes vasodilatation by increased synthesis of nitric oxide. Its production by different cells such as cardiac myocytes, smooth muscle, endothelial, and oncogenic cells is stimulated by inflammatory processes. It has been shown that in the presence of inflammation in the urinary system, concentration of AM increases. In this study, we measured urinary AM in children with acute pyelonephritis before and after treatment and compared its level with that in healthy children. MATERIALS AND METHODS: In a case-control study, 31 children with clinical and paraclinical documentation of pyelonephritis (case group) and 30 healthy children without pyelonephritis or other infections (control group) were studied. Urinary AM were measured on spot urine samples by high-performance liquid chromatography, and creatinine was measured by spectrophotometry to report the AM-creatinine ratio. RESULTS: Urinary AM-creatinine ratios were 61.3 +/- 119.4 pg/mg and 4.26 +/- 11.4 pg/mg, respectively, in the case and control groups (P = .01). After treatment of pyelonephritis in the patients of the case group, this ratio decreased to 13.1 +/- 21.9 (P = .048). The coefficient correlation between urinary AM and leukocytes count was 0.252 (P = .17). Urinary AM levels were 1896 +/- 1748 pg/dL and 391 +/- 477 pg/dL in the patients with 4+ versus negative C-reactive protein levels, respectively (P = .008). CONCLUSIONS: Urinary AM increases in the course of pyelonephritis and decreases significantly after treatment.

Kidney is in trouble with mediators.

The kidneys receive 20-25 % of cardiac output and play a main role in the control of cardiovascular homeostasis. It is an endocrine organ that regulates and produces many substances, scavenger particles and immune complexes. Cytokines, growth factors, reactive oxygen metabolites, bioactive lipids, proteases, vasoactive substances such as nitric oxide (NO), adrenomedullin (AM), urotensin-II (U-II), have been released in several diseases, and kidney is one of mostly affected organs in body. Some of these mediators act in a paracrine fashion while some act in autocrine. They play important roles in modulating the cardiovascular responses, renal hemodynamics, and probably in mediating the clinical and laboratory manifestations of several renal diseases. These mediators are like "a double edged sword". While small amounts of them mediate many physiological events, little excess may cause the damage to the healthy cells. Many investigators have searched the role(s) of mediators in several diseases. However, the findings are mostly like the model of "chicken and egg", and indistinguishable as to whether they are the causes of, or results of the diseases. We will discuss mainly the possible roles of NO, AM and U-II in children with several renal diseases and summarize what is known, and what must be known about these mediators.

Adrenomedullin gene expression and peptide levels in the heart and blood vessels of streptozotocin-diabetic rats.

The aim of the present study was to assess the changes in gene expression and peptide adrenomedullin (AM) levels in cardiovascular and other tissues in the streptozotocin-diabetic rats. For this purpose, diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/Kg body weight). Half of the diabetic rats were subcutaneously injected with insulin in the afternoon (4 units/day) one week after STZ injection until the day before killing. Control rats received only saline injection. AM mRNA was determined in cardiovascular and other tissues of streptozotocin-diabetic rats using solution-hybridization-RNase protection assay. Circulating AM and peptide AM in cardiovascular and other tissues were estimated using a specific radioimmunoassay. There were increases in preproAM mRNA levels in the left and right ventricles and in the thoracic aorta in both the 2-week and 4-week diabetic rats, but not in the two atria, the mesenteric artery and the lung. In the 2-week diabetic rats, there were decreases in AM contents in the two atria and the lung but an increase in the thoracic aorta. In the 4-week diabetic rats, there were bigger decreases in the atria and also a decrease in the left ventricle. The plasma AM levels were not changed but there was an increase in the excretion of AM in the urine. Our results suggest a possible increase in AM release in the heart and the thoracic aorta in the 2-week and 4-week diabetic rats.